Effect of gallbladder hypomotility on cholesterol crystallization and growth in CCK-deficient mice.

Effect of gallbladder hypomotility on cholesterol crystallization and growth in CCK-deficient mice.
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DOI:
10.1016/j.bbalip.2009.10.003
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发表时间:
2010-02
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Wang DQ
Wang DQ
中科院分区:
其他
文献类型:
--
作者:
Wang HH;Portincasa P;Liu M;Tso P;Samuelson LC;Wang DQ

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我们研究了 CCK 敲除小鼠胆囊运动不足对胆结石形成早期阶段胆固醇结晶和生长的影响。与野生型小鼠相反,在进食或生石饮食的基因敲除小鼠中,空腹胆囊体积增大,胆囊排空对高脂肪膳食的反应受损。在成石状态下,首先形成大量的粘蛋白凝胶和液晶以及弧状和管状晶体,然后在基因敲除小鼠中快速形成经典的平行四边形一水胆固醇晶体。此外,观察到晶体生长习性的三种模式:比例增大、螺旋位错生长和孪晶生长,所有这些都使固体胆固醇晶体增大。在采用生石饮食的第 15 天,75% 的基因敲除小鼠形成了胆结石。然而,野生型小鼠形成很少的粘蛋白凝胶、液体和固体晶体,并且没有观察到胆结石。我们得出的结论是,缺乏 CCK 会导致胆囊动力低下,从而延长过量胆固醇在胆囊中的停留时间,导致固体胆固醇晶体快速结晶和沉淀。此外,在胆结石形成的早期阶段,有两种液态和多晶型无水晶体演化为一水合物晶体的途径和三种胆固醇晶体生长模式。
We investigated the effect of gallbladder hypomotility on cholesterol crystallization and growth during the early stage of gallstone formation in CCK knockout mice. Contrary to wild-type mice, fasting gallbladder volumes were enlarged and the response of gallbladder emptying to a high fat meal was impaired in knockout mice on chow or the lithogenic diet. In the lithogenic state, large amounts of mucin gel and liquid crystals as well as arc-like and tubular crystals formed first, followed by rapid formation of classic parallelogram-shaped cholesterol monohydrate crystals in knockout mice. Furthermore, three patterns of crystal growth habits were observed: proportional enlargement, spiral dislocation growth, and twin crystal growth, all enlarging solid cholesterol crystals. At day 15 on the lithogenic diet, 75% of knockout mice formed gallstones. However, wildtype mice formed very little mucin gel, liquid and solid crystals, and gallstones were not observed. We conclude that lack of CCK induces gallbladder hypomotility that prolongs the residence time of excess cholesterol in the gallbladder, leading to rapid crystallization and precipitation of solid cholesterol crystals. Moreover, during the early stage of gallstone formation, there are two pathways of liquid and polymorph anhydrous crystals evolving to monohydrate crystals and three modes for cholesterol crystal growth.
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